The purpose of this study is to determine the risks of acquiring hepatitis C virus (HCV) infection associated with specific injection practices in a cohort of young, high-risk injection drug users (IDUs) on the Lower East Side of Manhattan, and the possible protective effect of pre-existing HCV-specific immune responses. Hepatitis C is the most rapidly rising opportunistic infection in persons with human immunodeficiency virus (HIV) infection and already the leading cause of death in persons with HIV/HCV co-infection. Because it is more prevalent and more readily transmitted among IDUs than HIV, HCV prevention serves as a sensitive model for the prevention of HIV and other bloodborne infections among IDUs. Despite advances in our understanding of HCV and its transmission, HCV continues to spread rapidly among IDUs, who now account for most new HCV infections in the developed world. A better understanding of the risks associated with the sharing of syringes and other injection equipment and many other opportunities for blood contact that arise during the preparation and injection of drugs is needed to guide the development of more effective prevention interventions. The proposed study will interview 100 high-risk, HCV-uninfected IDUs every two weeks and collect detailed information about their injection practices in order to examine the risks associated with specific injection practices. The specific aims are to: (1) Determine the specific injection practices associated with an increased risk of HCV infection, and estimate for each (a) the magnitude of the risk, (b) the dose-response relationship, and (c) the per-act transmission rate; (2) Examine how a prolonged period of frequent interaction with a research interviewer affects the relative performance of interviewer- vs. computer- administered questions; (3) Examine the impact of certain contextual factors characterizing injection settings on injection practices and HCV transmission; and (4) 4. Examine whether HCV-specific cellular immune responses observed in subjects at baseline exert a protective effect, and estimate the strength of any such effect. The findings from this study will help guide the development of evidence-based HCV prevention interventions, permit more accurate modeling of the HCV epidemic, and enhance our understanding of HCV- specific immunity.